Inactivation of the 14-3-3 sigma gene is associated with 5' CpG island hypermethylation in human cancers.
Inactivation of the 14-3-3 sigma gene is associated with 5' CpG island hypermethylation in human cancers.
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发表时间：
2000-08
期刊：
影响因子：
11.2
通讯作者：
Hiromu Suzuki;F. Itoh;M. Toyota;T. Kikuchi;H. Kakiuchi;K. Imai
中科院分区：
文献类型：
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作者：
Hiromu Suzuki;F. Itoh;M. Toyota;T. Kikuchi;H. Kakiuchi;K. Imai
细胞周期检查点在维持细胞的完整性方面起着重要作用。最近，14-3-3蛋白家族成员之一，14-3-3sigma，被证明受p53调节，并在G2-M期检查点中发挥作用。为了确定14-3-3sigma在人类癌症中是否失活，在一系列胃癌、结肠直肠癌和肝细胞癌细胞系中研究了14-3-3sigma的5'区域的甲基化状态。在检测的22个细胞系中，6个显示异常甲基化。发现14-3-3sigma的甲基化状态与表达丧失相关，其通过5-氮杂-2 '-脱氧胞苷处理恢复。此外，在甲基化的细胞系中没有证明DNA损伤后的正常G2期阻滞。在原发性胃癌中，26/60例（43%）病例中经常观察到14-3-3sigma高甲基化，在低分化腺癌中观察到更频繁（P = 0.0017）。我们的研究结果表明，14-3-3sigma在各种人类癌症中由于5'区域的异常甲基化而失活，并且它可能在未分化胃癌的发展中起重要作用。
The cell cycle checkpoint plays an important role in maintaining the integrity of cells. Recently, one of the 14-3-3 protein family members, 14-3-3sigma, was shown to be regulated by p53 and to play a role in the G2-M-phase checkpoint. To determine whether 14-3-3sigma is inactivated in human cancers, the methylation status of the 5' region of 14-3-3sigma was investigated in a series of gastric, colorectal, and hepatocellular cancer cell lines. Of 22 cell lines examined, 6 showed aberrant methylation. The methylation status of 14-3-3sigma was found to be correlated with loss of expression, which was restored by 5-aza-2'-deoxycytidine treatment. Furthermore, normal G2 arrest after DNA damage was not demonstrated in the cell lines with methylation. In primary gastric cancers, 14-3-3sigma hypermethylation was observed frequently in 26 of 60 (43%) cases and observed more frequently in poorly differentiated adenocarcinomas (P = 0.0017). Our findings suggest that 14-3-3sigma is inactivated by aberrant methylation of the 5' region in various human cancers and that it might play an important role in the development of undifferentiated gastric cancers.